An inherited single nucleotide variant (SNV) in the 5′UTR of the BRCA1 gene c.-107A > T was identified to be related to BRCA1 promoter hypermethylation and a hereditary breast and ovarian cancer phenotype in two UK families. We investigated whether this BRCA1 variant was also present in a Dutch cohort of breast and ovarian cancer patients with tumor BRCA1 promoter hypermethylation. We selected all breast and ovarian cancer cases that tested positive for tumor BRCA1 promoter hypermethylation at the Netherlands Cancer Institute and Sanger sequenced the specific mutation in the tumor DNA. In total, we identified 193 tumors with BRCA1 promoter hypermethylation in 178 unique patients. The wild-type allele was identified in 100% (193/193) of sequenced tumor samples. In a large cohort of 178 patients, none had tumors harboring the previously identified c.-107A > T SNV in BRCA1. We therefore can conclude that the germline SNV is not pervasive in patients with tumor BRCA1 promoter hypermethylation.

BRCA1基因 c.-107A > T的 5'UTR 中的遗传性单核苷酸变异 (SNV)被鉴定为与两个英国家庭中的BRCA1启动子高甲基化和遗传性乳腺癌和卵巢癌表型有关。我们研究了这种BRCA1变体是否也存在于荷兰乳腺癌和卵巢癌患者队列中，这些患者具有肿瘤BRCA1启动子高甲基化。我们选择了荷兰癌症研究所肿瘤BRCA1启动子高甲基化测试呈阳性的所有乳腺癌和卵巢癌病例，Sanger 对肿瘤 DNA 中的特定突变进行了测序。我们总共鉴定了 193 个带有BRCA1 的肿瘤178 名独特患者的启动子高甲基化。野生型等位基因在 100% (193/193) 的测序肿瘤样本中被鉴定出来。在 178 名患者的大型队列中，没有一例患者的肿瘤携带先前在BRCA1中发现的 c.-107A > T SNV 。因此，我们可以得出结论，种系 SNV 在肿瘤BRCA1启动子高甲基化患者中并不普遍。